Transcriptome and Mutant Analysis of Neuronal Genes for Memory Formation and Retrieval in Caenorhabditis elegans
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PROVIDER: PRJNA1016380 | ENA |
REPOSITORIES: ENA
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Project description:Although it is generally believed that the formation and retrieval of memory require distinct sets of genes, little is known about the identity and temporal specificity of genes that act at different memory stages. Here we characterize the transcriptomes for the formation and retrieval of stress-induced aversive memory in the nematode Caenorhabditis elegans. Our RNA-sequencing analysis show that neuronal genes for calcium homeostasis, membrane excitability, synaptic function and signaling are progressively activated during the formation of aversive memory. Stage-specific transcriptomes further reveal that memory formation and retrieval display distinct gene activation patterns. We carried out a candidate screen of mutants for these memory genes and verified the temporal requirement of memory function for several of them. Further in-depth characterization of casy-1/calsyntenin show that while the short CASY-1B isoform acts in memory retrieval, the long CASY-1A isoform functions during memory formation, and its shed extracellular N-terminus fragment is likely a critical signal for memory regulation. Our work uncovers gene expression patterns associated with distinct memory stages and provides a foundation for future mechanistic interrogation of memory functions.
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2016-06-25 | E-GEOD-83718 | biostudies-arrayexpress
Project description:Reward-related memory is an important factor in cocaine seeking. One necessary signaling mechanism for long-term memory formation is the activation of poly(ADP-ribose) polymerase-1 (PARP-1), via poly(ADP-ribosyl)ation. We demonstrate herein that auto-poly(ADP-ribosyl)ation of activated PARP-1 was significantly pronounced during retrieval of cocaine-associated contextual memory, in the central amygdala (CeA) of rats expressing cocaine-conditioned place preference (CPP). Intra-CeA pharmacological and shRNA depletion of PARP-1 activity during cocaine-associated memory retrieval abolished CPP. In contrast, PARP-1 inhibition after memory retrieval did not affect CPP reconsolidation process and subsequent retrievals. Chromatin Immuoprecipitation (ChIP) sequencing revealed that PARP-1 binding in the CeA is highly enriched in genes involved in neuronal signaling. We identified amongst PARP targets in CeA a single gene, yet uncharacterized and encoding a putative transposase inhibitor, at which PARP-1 enrichment dramatically increases during cocaine-associated memory retrieval and positively correlates with CPP. Our findings have important implications for understanding drug-related behaviors, and suggest possible future therapeutic targets for drug abuse.
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Project description:Neurons are categorised into many subclasses, and each subclass displays different morphology, expression patterns, connectivity and function. Changes in protein synthesis are critical for neuronal function. Therefore, analysing protein expression patterns in individual neuronal subclass will elucidate molecular mechanisms for memory and other functions. In this study, we used neuronal subclass-selective proteomic analysis with cell-selective Bio-Orthogonal Non-Canonical Amino acid Tagging (BONCAT). We selected Caenorhabditis elegans as a model organism because it shows diverse neuronal functions and simple neural circuitry. We performed proteomic analysis of all neurons or AFD subclass neurons that regulate thermotaxis in C. elegans. Mutant phenylalanyl tRNA synthetase (MuPheRS) was selectively expressed in all neurons or AFD subclass neurons, and azido-phenylalanine was incorporated into proteins in cells of interest. Azide-labelled proteins were enriched and proteomic analysis was performed. We identified 4412 and 1834 proteins from strains producing MuPheRS in all neurons and AFD subclass neuron, respectively. F23B2.10 (RING-type domain-containing protein) was identified only in neuronal cell-enriched proteomic analysis. We expressed GFP under the control of the 5' regulatory region of F23B2.10 and found GFP expression in neurons. We expect that more single-neuron specific proteomic data will clarify how protein composition and abundance affect characteristics of neuronal subclasses.
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Project description:The immune and nervous systems are highly interactive, however, little is known about how immune cells and their derived molecules impact brain function. Here we show that T cells play a critical role in retrieval of contextual fear conditioning (CFC) memory. Single-nuclei sequencing (snRNAseq) of engram neurons and non-engram neurons from the dentate gyrus one day after CFC learning revealed new evidence about differential expression of immune-related and synaptic plasticity-related genes, in SCID vs. wild-type mice. These findings present a comprehensive picture on how T cells and their derived cytokines could regulate memory retrieval and provide new insights into the nature of neuroimmune interactions at the transcriptional level in neurons. Overall, restoration of T cells or IL-4R signaling might lead to selective rescue of memory retrieval, and proffer a valuable strategy for treating memory loss.
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Project description:Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of the 1H channel in learning and memory, we subjected Cav3.2 homozygous, heterozygous knockout and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning (TFC), the Morris water-maze and passive avoidance. The Cav3.2-/- mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2+/- mice, whereas LTP persisted for only 120 minutes in Cav3.2-/- mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes , we next performed experiments locally knock down function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil exhibited similar behaviors as homozygous knockouts. Finally, microarray analyses indicated that Cav3.2-/- and WT mice presented distinct hippocampal transcriptome profiles. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel. After WT and Cav3.2 KO mice retrieval of context-associated memory, three right hippocampi of each group were dissected, pooled together and homogenized. The products of experimental and naive groups were used to acquire expression profiles of a total of 29,922 unique genes. Two replicates per group.
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